GLUTEN AND

CELIAC DISEASE

CHARLENE LEPANE, D.O., FACOI, FACG

**NO DISCLOSURES**

GLUTEN

From Latin gluten, "glue"

Protein composite found in wheat and related grains,

including barley and rye (oats can be tolerated by most but

cross-contamination or hypersensitivity may limit tolerability)

Gluten is the composite of the storage proteins, gliadin and

a glutenin

Conjoined with starch in the endosperm of various grass-

related grains

True gluten, with gliadin and glutenin, is limited to certain

members of the grass family

GLUTEN

Bread flours are high in gluten

Pastry flours have a lower gluten content

Gluten is often the basis for imitation meats

Gluten is often present in beer and soy sauce

Stabilizing agent in food products such as ice

cream and ketchup

Gluten is also used in cosmetics, hair products,

and other dermatological preparations

DEFINITIONS

Non-celiac gluten sensitivity(gluten intolerance)

Wheat allergy

Celiac disease (gluten sensitivity)

* No evidence suggests negative side effects occur with gluten consumption outside of the small percentage of the population having gluten sensitivity

NON-CELIAC GLUTEN SENSITIVITY

(GLUTEN INTOLERANCE)

Syndrome of gastrointestinal responses to gluten different

from the immune response characteristic of celiac disease

No scientific consensus exists to confirm gluten intolerance

is a definable pathological condition

Frequently, symptoms arise in individuals as a result of

undiagnosed celiac disease

Due to a reaction to other components of wheat, such as

short-chain, fermentable carbohydrates called FODMAPs

Fermentable

Oligo-, Di-, Mono-

saccharides

and Polyols

WHEAT ALLERGY

A wheat allergy causes the immune system

to abnormally respond to a component of

wheat that it treats as a threatening foreign

body

This immune response is often self-limiting and

does not cause lasting harm to body tissue

Wheat allergy and celiac disease are

different disorders

CELIAC DISEASE

First described by Samuel Gee in 1888

Recognized by Dutch pediatrician WWII food

shortage

Celiac lesion in proximal small bowel first described

1954

Intestinal reaction to alpha-gliadin in gluten resulting

in a loss of intestinal villi and a disruption of absorption

Gluten sensitive enteropathy, also called nontropical

sprue

CELIAC DISEASE

Classic definition includes the following three

features:

Villous atrophy

Symptoms of malabsorption such as

steatorrhea, weight loss or other signs of nutrient

or vitamin deficiency

Resolution of the mucosal lesions and symptoms

upon withdrawal of gluten-containing foods

(usually weeks to months)

CELIAC DISEASE: EPIDEMIOLOGY

Multisystem disease

1% or 1/133 persons of US

1:70 to 1:300 in most countries

Primarily in whites of Northern European

ancestry

Not specific to age or gender

Familial (70% twins and 10% first degree family

member)

CELIAC DISEASE: GENETICS Intra familial occurrence and close association with HLA-DQ2

and/or DQ8 gene loci provide basis of current understanding

Immune disorder triggered by an environmental agent

(gliadin) in genetically predisposed individuals

HLA-DQ2 (95% of patients) and HLA-DQ8 (5% of patients);

Absence of the DQ gene rules out celiac disease with 99%

confidence

Presence of one of these markers is necessary but not

sufficient for diagnosis

DQ2 and 8 are present in 30-40% of the general Western

population, suggesting other factors play a role

CELIAC DISEASE

Associated disorders (many autoimmune)

Endocrine (DM I, autoimmune thyroid,

Addison’s, Osteopenia)

Mixed connective tissue disease (Sjogren's, RA)

Cardiopulmonary (Asthma, Sarcoid, Carditis,

pulmonary hemosiderosis, fibrosing alveolitis)

Neurological (Seizures, Dementia, Peripheral

neuropathy, Psychiatric disorders)

CELIAC DISEASE

Associated disorders (many autoimmune)

Skin (Dermatitis, Atopy, Psoriasis)

Malignancy (Lymphoma, Esophageal,

Oropharyngeal)

Gastrointestinal (GERD, EoE, IBD-UC>CD, microscopic

colitis)

Reproductive (Amenorrhea, Infertility, recurrent

spontaneous abortion)

Immunologid (IgA deficiency)

Down syndrome

CELIAC DISEASE:

CLINICAL MANIFESTATIONS

May be confused with IBS due to non-specific symptoms

Malabsorption (diarrhea, foul smelling stools, weight loss, cramps,

fatigue)

Multisystemic

Oral (dental enamel, apthous ulcerations)

Labs (IDA, elevated transaminases ALT>AST (~42% of pts with

celiac and normalize with gluten free diet), low albumin)

Dermatitis herpetiformis

Neuropsychiatric disease (HA, peripheral neuropathy, ataxia,

depression, anxiety, epilepsy)

CELIAC DISEASE:

CLINICAL MANIFESTATIONS

Higher prevalence osteoarthritis (relationship unknown)

Metabolic bone disease (osteopenia and osteoporosis)

Secondary hyperparathyroidism likely d/t vit D deficiency

Hyposplenism (mechanism unknown)

Prophylactic pneumococcal vaccination suggested

Kidney disease- glomerular IgA deposition, but rarely have

manifestations

Idiopathic pulmonary hemosiderosis (Lane-Hamilton syndrome)

Introduction of gluten-free diet assoc with remission of

pulmonary symptoms

DENTAL ENAMEL HYPOPLASIA

DERMATITIS HERPETIFORMIS

Intensely pruritic

papulovesicular rash

Typically on extensor surface

Represents intestinal sensitivity

to gluten

Biopsy show granular IgA

deposits in the papillary dermis

(pathognomonic)

Responds to gluten-free diet

Dapsone may help with

healing of skin

DERMATITIS HERPETIFORMIS

CELIAC DISEASE: LABORATORY STUDIES

Anti Gliadin IgG: 75% sensitivity, 97% specificity

May also be found in 10-20% of patients with other disease that

affect the small intestinal mucosa

Helpful for monitoring outcome: always becomes negative with

the regrowth of jejunal villi in patients after gluten-free diet

Anti Endomysial IgA: 97-100% specificity, 85% sensitivity

(untreated patients)

Can persist in low titers in 10-25% of patients who are treated

despite normal histology, or become negative with adherence

to gluten-free diet

CELIAC DISEASE: LABORATORY STUDIES

Anti-transglutaminase IgA (tTG IgA): 100% specificity,

90% sensitivity - best sensitivity and specificity

Endomysial and transglutaminase can be false

negative in those with IgA deficiency

(approximately 2.5% of the population; therefore IgA

level should always be ordered with serology) and

children less than 2 years old

Any serological tests for celiac disease should be

confirmed with a small bowel biopsy

CELIAC DISEASE ENDOSCOPY

AND HISTOLOGY

CELIAC DISEASE: HISTOLOGY

CELIAC DISEASE: HISTOLOGY

Modified Marsh Classification

Type 1: increased

intraepithelial

lymphocytes but no

villous atrophy

Type 2: villi still present but

shortened

Type 3: mild to marked

villous atrophy

Type 4: lamina propria

hypoplasia; no villi

CELIAC DISEASE: TREATMENT

Gluten-free diet: removal of wheat, rye and barley; Nutrition consult for education

Oats do not contain gluten but are often contaminated with gluten during processing

Rice, corn, and millet do not contain gluten

Lactose-free diet initially (the brush border contains lactate which is not functional with sprue)

Those with continued diarrhea should be examined for other causes of diarrhea

DDX of non-responders:

Incorrect diagnosis (IBS), Continuing gluten intake (restaurants), SBBO, IBD/Microscopic colitis, Pancreatic insufficiency, lactase deficiency, Lymphoma, Autoimmune enteropathy, Refractory sprue (rare)

CELIAC DISEASE: COMPLICATIONS

Malignancy: Squamous cell cancer of

esophagus, Small bowel adenocarcinoma,

Intestinal and extraintestinal lymphoma (T-cell)

Rarely a functional asplenia can occur,

consider Pneumovax

Risk of untreated Celiac disease: Infertility,

Miscarriage, Epilepsy, Intestinal Lymphoma

CELIAC DISEASE: COMPLICATIONS

Conditions to consider if previously responsive

patients begin to deteriorate:

Noncompliance: with gluten-free diet (most

common)

Lymphoma (T-Cell): most common malignancy

complicating celiac disease; Requires high index of

suspicion

Think about in patients not responding to diet therapy or

recurrent weight loss despite diet therapy

EGD, CT & exploratory laparotomy may be necessary

CELIAC DISEASE: COMPLICATIONS

Refractory Sprue: Patients do not respond to

gluten-free diet, either at onset of diagnosis or

becoming refractory with diet adherence

No other cause found after thorough investigation

Some respond to steroids, azathioprine and

cyclosporine

Severe complications include ulcerative jejunitis,

collagenous sprue, and lymphoma

CELIAC DISEASE: COMPLICATIONS

Collagenous Sprue: subset of Refractory

Sprue; Usually refractory to all forms of

therapy other than parenteral alimentation

Characterized by development of thick band of

collagen-like material

Other malignancies with increased risk

Non-Hodgkin’s lymphoma

Small bowel adenocarcinoma

Oropharyngeal and esophageal cancers

LEARN MORE ABOUT CELIAC DISEASE

Celiac Disease Symptoms and

Conditions Checklist

What is Celiac Disease?

Dermatitis Herpetiformis

Gluten Sensitivity

Diagnosing Celiac Disease

Screening Diagnosis

Treatment and Follow Up

Poorly Responsive Celiac Disease

Celiac Disease and Vaccinations

Celiac Disease and Diabetes

Celiac Disease and Crohn’s Disease

Future Therapies for Celiac Disease

Research

Research Studies

Celiac Disease in the News

Celiac Disease

Foundation

Featured in Time

Magazine

July 30, 2015

https://celiac.org

CELIAC DISEASE FOR PRACTITIONERS

https://celiac.org/celiac-disease/provider-directory

Be Listed in the CDF Healthcare Practitioner Directory

Earn CME in Celiac Disease

Earn CME in Gluten-Related Disorders

THANK YOU clepane@hotmail.com